PMID- 10490106 OWN - NLM STAT- MEDLINE DCOM- 19991001 LR - 20220318 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 98 IP - 5 DP - 1999 Sep 3 TI - Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. PG - 675-86 AB - Nuclear receptors have been postulated to regulate gene expression via their association with histone acetylase (HAT) or deacetylase complexes. We report that hormone induces dramatic hyperacetylation at endogenous target genes through the HAT activity of p300/CBP. Unexpectedly, this hyperacetylation is transient and coincides with attenuation of hormone-induced gene activation. In exploring the underlying mechanism, we found that the acetylase ACTR can be acetylated by p300/CBP. The acetylation neutralizes the positive charges of two lysine residues adjacent to the core LXXLL motif and disrupts the association of HAT coactivator complexes with promoter-bound estrogen receptors. These results provide strong in vivo evidence that histone acetylation plays a key role in hormone-induced gene activation and define cofactor acetylation as a novel regulatory mechanism in hormonal signaling. FAU - Chen, H AU - Chen H AD - The Salk Institute for Biological Studies, La Jolla, California 92037, USA. FAU - Lin, R J AU - Lin RJ FAU - Xie, W AU - Xie W FAU - Wilpitz, D AU - Wilpitz D FAU - Evans, R M AU - Evans RM LA - eng GR - GM26444/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Histones) RN - 0 (Nuclear Proteins) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Recombinant Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (Trans-Activators) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.48 (Histone Acetyltransferases) SB - IM MH - Acetylation MH - Acetyltransferases/*metabolism MH - *Gene Expression Regulation MH - HL-60 Cells MH - Histone Acetyltransferases MH - Histones/agonists/*metabolism MH - Humans MH - Kinetics MH - Models, Genetic MH - Models, Molecular MH - Mutagenesis MH - Nuclear Proteins/metabolism MH - Receptors, Cytoplasmic and Nuclear/genetics/metabolism MH - Recombinant Proteins/metabolism MH - *Saccharomyces cerevisiae Proteins MH - Signal Transduction MH - Time Factors MH - Trans-Activators/metabolism MH - Transcriptional Activation EDAT- 1999/09/18 00:00 MHDA- 1999/09/18 00:01 CRDT- 1999/09/18 00:00 PHST- 1999/09/18 00:00 [pubmed] PHST- 1999/09/18 00:01 [medline] PHST- 1999/09/18 00:00 [entrez] AID - S0092-8674(00)80054-9 [pii] AID - 10.1016/s0092-8674(00)80054-9 [doi] PST - ppublish SO - Cell. 1999 Sep 3;98(5):675-86. doi: 10.1016/s0092-8674(00)80054-9.